This project advances the study of brain connectivity using diffusion imaging and its powerful extensions beyond the tensor model of diffusion (HARDl, multi-shell HYDI, DSI). An increasing number of our collaborators have been analyzing their DTI data with us. Our Aims are based on the tools they asked us to develop. As we began to publish our collaborative DTI work on HIV/AIDS (DBP2A/alcour), 22q deletion syndrome. Fragile X (DBPS/Simon), blindness (DBP14/Lepore) and bipolar illness (C&Si/Altshuler), many of our collaborators have been asking for the tools below. Our DBPs also provide unique data to help us: Jack (DBP12) sends us short-interval repeat scans with many different DTI protocols, to assess stability of DTI-derived measures; Wright (DBPS) sends us 4-Tesla 105-gradient HARDl and GWAS from 1150 twins, allowing us to test tools that discover genes influencing brain connectivity. Our basic DTI analysis pipeline is already used in many DBP projects and our Aims will expand it. One of our aims considers the genetic influences on brain connectivity. It merges exciting new concepts from genetics and imaging; this work is now leading to major discoveries of specific genes that affect brain integrity (DBPS; Wright; see Progress).